一株人源性高效尿酸降解菌M2a的分离鉴定、全基因组测序及功能分析

Isolation, identification, whole-genome sequencing, and functional analysis of a human-derived efficient uric acid-degrading bacterium M2a

摘要:

【背景】 高尿酸血症是一种尿酸生成与排泄失衡所导致的嘌呤代谢紊乱疾病，而肠道微生物在嘌呤代谢中发挥重要作用，其中1/3的尿酸通过肠道菌群分解，所以肠道益生菌能够有效降低体内尿酸水平，缓解高尿酸血症。【目的】 获得人源性尿酸降解菌，并了解其与尿酸降解有关的基因及功能。【方法】 通过体外尿酸强化培养和驯化，从正常低尿酸健康人群肠道粪便中获得具备尿酸降解能力的菌株，对其进行一般形态学观察、生化试验、16S rRNA基因序列测定，以及生物信息学分析和鉴定，并进行全基因组测序和功能基因挖掘。【结果】 分离出一株具有较高尿酸降解功能的革兰氏阳性杆菌M2a，尿酸降解率达到82.73%，经鉴定为类干酪乳酪杆菌(Lacticaseibacillus paracasei)，全基因组测序发现菌株M2a具有9个与尿酸降解相关的基因。【结论】 菌株M2a具有高效降解尿酸的能力，为开发和利用微生物制剂进行尿酸治疗提供了科学依据和菌种资源。

Abstract:

[Background] Hyperuricemia is a purine metabolism disorder caused by an imbalance between uric acid production and excretion. The gut microbiota plays a significant role in purine metabolism, degrading approximately one-third of uric acid. Accordingly, gut probiotics have garnered wide attention for their potential of lowering uric acid levels and alleviating hyperuricemia. [Objective] To isolate human-derived uric acid-degrading bacteria and identify the genes and functions potentially involved in uric acid degradation. [Methods] After in vitro enrichment and acclimatization with uric acid, a strain capable of degrading uric acid was isolated from the feces of healthy individuals with normal low uric acid levels. Morphological observation, biochemical tests, 16S rRNA gene sequencing, bioinformatics analysis, and identification were then carried out for this strain. In addition, whole-genome sequencing and functional gene mining were performed. [Results] A Gram-positive bacterium (M2a) with a high uric acid degradation rate of 82.73% was isolated and identified as Lacticaseibacillus paracasei. Whole-genome sequencing revealed that M2a carried nine genes associated with uric acid degradation. [Conclusion] M2a can efficiently degrade uric acid, providing a scientific basis and bacterial resource for the future development and utilization of microbial preparations for treating uric acid-related disorders.